Localization of MMR proteins on meiotic chromosomes in mice indicates distinct functions during prophase I

Nadine K. Kolas, Anton Svetlanov, Michelle L. Lenzi, Frank P. Macaluso, Steven M. Lipkin, R. Michael Liskay, John M. Greally, Winfried Edelmann, Paula E. Cohen

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

Mammalian MutL homologues function in DNA mismatch repair (MMR) after replication errors and in meiotic recombination. Both functions are initiated by a heterodimer of MutS homologues specific to either MMR (MSH2-MSH3 or MSH2-MSH6) or crossing over (MSH4-MSH5). Mutations of three of the four MutL homologues (Mlh1, Mlh3, and Pms2) result in meiotic defects. We show herein that two distinct complexes involving MLH3 are formed during murine meiosis. The first is a stable association between MLH3 and MLH1 and is involved in promoting crossing over in conjunction with MSH4-MSH5. The second complex involves MLH3 together with MSH2-MSH3 and localizes to repetitive sequences at centromeres and the Y chromosome. This complex is up-regulated in Pms2-/- males, but not females, providing an explanation for the sexual dimorphism seen in Pms2-/- mice. The association of MLH3 with repetitive DNA sequences is coincident with MSH2-MSH3 and is decreased in Msh2-/- and Msh3-/- mice, suggesting a novel role for the MMR family in the maintenance of repeat unit integrity during mammalian meiosis.

Original languageEnglish (US)
Pages (from-to)447-458
Number of pages12
JournalJournal of Cell Biology
Volume171
Issue number3
DOIs
StatePublished - Nov 7 2005

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Meiotic Prophase I
DNA Mismatch Repair
Chromosomes
Nucleic Acid Repetitive Sequences
Meiosis
Proteins
Centromere
Y Chromosome
Sex Characteristics
Genetic Recombination
Maintenance
Mutation
MutL Proteins

ASJC Scopus subject areas

  • Cell Biology

Cite this

Localization of MMR proteins on meiotic chromosomes in mice indicates distinct functions during prophase I. / Kolas, Nadine K.; Svetlanov, Anton; Lenzi, Michelle L.; Macaluso, Frank P.; Lipkin, Steven M.; Liskay, R. Michael; Greally, John M.; Edelmann, Winfried; Cohen, Paula E.

In: Journal of Cell Biology, Vol. 171, No. 3, 07.11.2005, p. 447-458.

Research output: Contribution to journalArticle

Kolas, Nadine K. ; Svetlanov, Anton ; Lenzi, Michelle L. ; Macaluso, Frank P. ; Lipkin, Steven M. ; Liskay, R. Michael ; Greally, John M. ; Edelmann, Winfried ; Cohen, Paula E. / Localization of MMR proteins on meiotic chromosomes in mice indicates distinct functions during prophase I. In: Journal of Cell Biology. 2005 ; Vol. 171, No. 3. pp. 447-458.
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